Secondary metabolites from marine-associated actinomycetes are important source for the discovery of novel bioactive compounds. In this study, an actinomycete Streptomyces sp. ZZ446 was isolated from coastal soils and different media were used to culture this isolated marine actinomycete. It has been found that this actinomycete in the liquid medium of 2216 E with sea salt produced five new compounds of streptopyrazinones AD (1e4) and N-acetyl-L-isoleucine-L-leucinamide (5) as well as six known diketopiperazines (6e11) and one alkaloid (12). Structures of the new compounds were determined by extensive NMR analyses, HRESIMS data, electronic circular dichroism (ECD) calculation, chemical degradation, Marfey's method, and X-ray diffraction analysis. This type of streptopyrazinones AD (1e4) is rarely found in the natural resources. New compounds 1e5 showed activity in inhibiting the growth of Candida albicans and methicillin-resistant Staphylococcus aureus.